Granulocyte colony-stimulating factor (G-CSF) has a molecular weight of approximately 18,000 to 22,000. This factor is a glycoprotein, which induces the differentiation and proliferation of one type of a blood component leukocyte, neutrophil. This glycoprotein is comprised of 174 amino acids (occasionally 178 amino acids) in the case of human, and it is composed of 178 amino acids in the case of mouse.
G-CSF affects to enhance the survival and function of mature neutrophils, the formation of erythroblasts by an erythropoietin, and the formation of blast cell colonies by interleukin-3. Moreover. G-CSF promotes (reinforces the function and increases the numbers of) blood cells such as leukocytes, erythrocytes or thrombocytes. Examples of the cells generating G-CSF include macrophages, stromal cells, monocytes, T lymphocytes, fibroblasts, vascular endothelial cells and others.
Administration of G-CSF as a therapuetic agent has an effect for treatment of neutropenia as a side effect of an anticancer agent, neutropenia occurring after bone marrow transplantation, and aplastic anemia. However, when G-CSF is administered, it requires frequent administration because of its low stability in the blood, and further, the administration route is limited to intravenous or subcutaneous administration. Therefore, the use of G-CSF as a therapeutic agent is painful for patients and imposing the burden to doctors. Moreover, it has been reported that bone ache occurs as a side effect when G-CSF is therapeutically administered. Direct administration of macrophages or stroma cells, which produce G-CSF, has not been carried out, since these cells happen to contain various types of proteins or substances and so unexpected side effects might occur.
As stated above, a method of differentiating and growing neutrophils by the direct administration of G-CSF elicits bone ache as a side effect and requires frequent administration, thereby giving a certain pain and burden to both patients and doctors. Accordingly, the development of another treatment method is strongly required, but it has not been established up till now.
Thus, the present inventors have intended that G-CSF is not directly administered but G-CSF is allowed to be produced and as a result neutrophils are differentiated and grown, and they have previously succeeded in providing a G-CSF-inducing antibody (Japanese Patent Application No. 9-266591 (Sep. 30, 1997) and Japanese Patent Laid-Open No. 11-106400 (Apr. 20, 1999). However, an antigen recognized by the G-CSF inducing antibody has not been clarified.